期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 47, 期 2, 页码 203-209出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.yjmcc.2009.04.010
关键词
Ankyrin; Cytoskeleton; Arrhythmia; Targeting; Trafficking
资金
- NIH [HL084583, HL083422, T32 HL07121]
- Pew Scholars Trust
- American Heart Association [0930378N]
Ankyrins are critical components of ion channel and transporter signaling complexes in the cardiovascular system. Over the past 5 years, ankyrin dysfunction has been linked with abnormal ion channel and transporter membrane organization and fatal human arrhythmias. Loss-of-function variants in the ankyrin-B gene (ANK2) cause ankyrin-B syndrome (previously called type 4 long QT syndrome). manifested by a complex cardiac phenotype including ventricular arrhythmias and sudden cardiac death. More recently, dysfunction in the ankyrin-B-based targeting pathway has been linked with a highly penetrant and severe form of human sinus node disease. Ankyrin-G (a second ankyrin gene product) is required for normal expression, membrane localization, and biophysical function of the primary cardiac voltage-gated sodium channel, Na(v)1.5. Loss of the ankyrin-G/Na(v)1.5 interaction is associated with human cardiac arrhythmia (Brugada syndrome). Finally, in the past year ankyrin dysfunction has been associated with more common arrhythmia and cardiovascular disease phenotypes. Specifically, large animal studies reveal striking remodeling of ankyrin-B and associated proteins following myocardial infarction. Additionally, the ANK2 locus has been linked with QT(c) interval variability in the general human population. Together, these findings identify a host of unanticipated and exciting roles for ankyrin polypeptides in cardiac function. More broadly, these findings illustrate the importance of local membrane organization for normal cardiac physiology. (C) 2009 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据